Polyarteritis nodosa

- Polyarteritis nodosa. This is a medium vessel vasculitis that affects many arteries. And so, if we break it down, we can see poly means many, arter refers to the arteries, and itis is inflammation, just like any vasculitis you see some inflammation, and nodosa means nodular. So, when you break this name down, we see that many arteries have inflammation and are nodular. So, why is it nodular? Well, to understand that, let's draw out a blood vessel. Remember that blood vessels are like pipes. They carry blood and distribute nutrients throughout the body. And so, here I'm shading in the wall of the blood vessel, and in the back, I'm kind of drawing this little circular appearance. I'm trying to show you it's a little bit of a 3D drawing. So, imagine you take a cross section through the blood vessel, right down the middle. So, you can see that blood and nutrients would travel down this blood vessel. So, remember with vasculitis the body is mistaking the blood vessels to be a foreign protein or something foreign, and so antibodies, little Y-shaped proteins that are released by the immune system, are targeting the blood vessel wall, because they think it's foreign. Remember, antibodies act as markers to draw in white blood cells to cause some damage to the area, because these white blood cells release molecules that are very destructive. The intent is to kill pathogens, but here you're accidentally killing the blood vessels. And so, one theory as to why the antibodies are accidentally targeting blood vessels is the theory of molecular mimicry, molecular mimicry. What is molecular mimicry? Well, it's the theory that foreign proteins, such as bacteria, viruses, or really anything bad, any pathogen that gets in your body, are recognized by the immune system. The immune system, of course, creates these antibodies to target these bad foreign proteins. And so, this is good. This is what antibodies are used for. They're supposed to target foreign proteins, to mark them for destruction for white blood cells, but in the process of recognizing these foreign proteins, many antibodies are created. So now the immune system is ramping up to find and seek out these foreign proteins if they ever appear again. Now the idea of molecular mimicry is that there are self proteins, such as maybe proteins from the blood vessel walls, that look identical to foreign proteins. Now, I know I've drawn them as little circles here, but let's say that they're identical, and these antibodies that were created in response to these foreign proteins now also are recognizing self proteins, because the self looks very similar to these foreign proteins. This is the core of molecular mimicry. In polyarteritis nodosa, hepatitis B is actually found in about 20 to 30% of patients, so it's believed that maybe hepatitis B, the proteins that are in this virus, can cause a molecular mimicry and look very identical to self, and so these foreign hepatitis B molecules look like self and induce this entire autoimmune destruction of blood vessels. And so, that's why I make this point of molecular mimicry. Now, in polyarteritis nodosa, again white blood cells release all these immune peptides and cause destruction of the blood vessel wall. Damage to the wall causes molecules like collagen and tissue factor, which are normally not exposed to blood, to be released, and when they're released, they interact with clotting factors in the blood, such as fibrin. Fibrin reacts with the stuff in the wall of the blood vessels and creates a net-like mesh. This net-like mesh is a clot. So, fibrin is integral in clot formation. Another word you might hear for clot is thrombosis. Thrombosis is the formation of clots. And so, along with this acute inflammation and clot formation, you can also have old wounds in blood vessels, where the fibrin has already tried to patch up the wall. Now, this wall right here is very weak, and so the vessels go through this damage over and over again, and the blood vessel wall continues to weaken. Now blood vessels, obviously, are just like pipes, and they're used to carry blood downstream. If red blood cells, or any other contents, hit the wall of the blood vessel, they're supposed to bounce off and just continue on their merry way. But the problem here is with a weakened blood vessel, when red blood cells push against this, the wall is so weak that it bulges out. This bulging of the blood vessel wall is called an aneurysm. It's a weakened part of the wall that bulges out from the pressure on the inside of the blood vessel. And lastly, if the blood vessel wall weakens so much and receives way too much pressure, it can rupture, and this allows blood to spill out of the blood vessel. In medium size blood vessels, rupture of this can cause a lot of bleeding, and so rupture is a feared complication of polyarteritis nodosa. Now, if you were to take a slice of this blood vessel wall and take a look at it under a microscope, you'd be taking a biopsy. That's what a biopsy is, a slice of tissue that you take a look at under a microscope. And so, in polyarteritis nodosa, we see this fibrinoid necrosis. There are fibrin clots in the wall of blood vessels and a lot of debris in there too and cells that are dead. And so, you go through fibrinoid necrosis, and the blood vessels also go through some scarring, so it's an attempt to try to heal. Once the scar is finished, once the blood vessel has been patched up, this is the process of healing, and so you continue to go through this cycle over and over and over again, and this continuous process will cause weakening of the blood vessel walls, and I make this point because the weakening can get very severe, and the blood vessels will bulge out, just like I was showing above. These aneurysms appear all throughout the blood vessel and give its classic appearance. So, this blood vessel wall bulge, blood vessel wall bulge, blood vessel wall bulge is noted to look like a string full of beads, and this is actually a classic appearance of polyarteritis nodosa, this beads on a string pattern. This pattern can be seen under a microscope, and it can also be seen when you take a look at an arteriogram. This picture right here is an arteriogram of the kidney. Here's the kidney right here. Kidneys kind of look like a kidney bean, right? And so, here's blood vessels that are going through, passing into the kidney, and if you look closely at the blood vessels, you can see some of these little dots that are in the blood vessels. These are the nodes. This is the nodularity. There's some here. There's some here. There's one right there. There's one over here. And this isn't very prominent. This arteriogram right here, which allows you to visualize the inside of the blood vessels, can actually show very severe aneurysms, very severe bulging of the blood vessel walls. And so, I'm exaggerating and showing these little black circles, and just like our beads on a string drawing above, you might see nodularity of the blood vessels like that, looking like a bead on a string pattern. And so, polyarteritis nodosa is infamous for causing a lot of damage to many different medium blood vessels all over the place, blood vessels in your intestines, blood vessels in the spleen, blood vessels in the kidneys, blood vessels of the skin, and it can actually commonly be in the legs as well, even blood vessels serving the nerves or the genitals or the heart. As you can guess, this causes a wide variety of symptoms. Not only will you get your generalized symptoms, such as fever, chills, and night sweats, just like any other vasculitis, but also you're getting local damage of organs. So, damage in the intestines may lead to bloody diarrhea. Damage to blood vessels supplying the skin may give you a sort of rash appearance and other skin lesions. These ulcers are formed because blood isn't supplying the skin as it should. Blood not supplying the heart can lead to heart attacks. The heart muscle won't contract anymore. If nerves don't get blood, you may see something called neuropathy. Neuropathy means neural pain or neural issues, and so you might not be able to move the foot as well, if the nerves supplying your foot is damaged, or you may feel a tingling sensation or decreased sensations in the foot. Lastly, I wanted to touch on the kidneys. When the kidneys receive very low blood volume, because remember, these arteries are being damaged and maybe on the inside it's very narrow, and so blood can't be delivered to the kidney tissue, when the kidney senses decreased blood volume, it thinks, oh, I need to increase pressure, and so, its sensation of low blood volume makes it go through the renin-aldosterone-angiotensin system. This system is the kidneys way to hold onto water and fluid, and so you get an increase in blood pressure. This increase in blood pressure, of course, is also known as hypertension. Now, how do you remember all of this? There's so many different vessels that are damaged. Among all the arteries that are damaged, pulmonary arteries, blood vessels supplying the lungs, are not damaged. We actually don't know why this is the case, but this ends up being a great mnemonic for you, to help you remember this. Polyarteritis nodosa, pulmonary arteries are not damaged. And treatment is done with two different medications. Steroids. Steroids inhibit the ability for white blood cells to communicate with other white blood cells. So, for example, here's a part of the blood vessel wall, and let's say this white blood cell wants to cause damage to this wall. It'll also recruit its buddies by sending these molecules to communicate and say, hey, come on over here. However, steroids shut down the communication creation of these immune molecules. These are called cytokines, by the way. It's a way for cells to communicate, and so, shutting this down prevents more white blood cells from being recruited to the blood vessel wall, which decreases the damage of this disease. And cyclophosphamide is the other medication that's used to treat this disease. Cyclophosphamide acts to cause damage to DNA. That seems very disastrous. The point of this medication is to target cells that rapidly divide. Immune cells actually go through rapid growth and division. You have new creation of immune cells every single day. So, by killing off some of these rapidly dividing cells, it slows down the immune system. So, by preventing the cells from causing damage, we slow down inflammation to arteries.